Ovarian cancer (OC) causes more deaths than any other cancer of the female reproductive system due to its late presentation and malignant nature. Although significant progress has been made in the diagnosis and treatment of OC over the last decade, chemotherapeutic drug resistance and cancer recurrence remain serious challenges in OC management. In the field of cancer therapy, traditional Chinese herbal medicines and their active compounds have been widely reported to have favorable therapeutic effects on cancer. Recent studies have also revealed the protective effect of puerarin in cancer, but the exact role and underlying mechanism of puerarin in OC remain unclear. Here, we established in vivo and in vitro OC models to evaluate the anticancer effect of puerarin. It was found that puerarin significantly inhibited OC cell viability and proliferation and induced cell apoptosis. In OC model mice, puerarin treatment suppressed tumor formation and modulated the gut microbiome. In addition, the expression of tumor suppressor genes was activated by puerarin in vitro and in vivo. These findings add to the existing knowledge on the usefulness of herbal active ingredients for the prevention and treatment of OC and provide a new perspective regarding the therapeutic potential of puerarin in cancer.

ObjectiveTo assess the predictive value of magnetic resonance imaging (MRI) radiomics for progression-free survival (PFS) in patients with prostate cancer (PCa).Methods191 patients with prostate cancer confirmed by puncture biopsy or surgical pathology were included in this retrospective study, including 133 in the training group and 58 in the validation group. All patients underwent T2WI and DWI serial scans. Three radiomics models were constructed using univariate logistic regression and Gradient Boosting Decision Tree(GBDT) for feature screening, followed by Cox risk regression to construct a mixed model combining radiomics features and clinicopathological risk factors and to draw a nomogram. The performance of the models was evaluated by receiver operating characteristic curve (ROC), calibration curve and decision curve analysis. The Kaplan-Meier method was applied for survival analysis.ResultsCompared with the radiomics model, the hybrid model consisting of a combination of radiomics features and clinical data performed the best in predicting PFS in PCa patients, with AUCs of 0.926 and 0.917 in the training and validation groups, respectively. Decision curve analysis showed that the radiomics nomogram had good clinical application and the calibration curve proved to have good stability. Survival curves showed that PFS was shorter in the high-risk group than in the low-risk group.ConclusionThe hybrid model constructed from radiomics and clinical data showed excellent performance in predicting PFS in prostate cancer patients. The nomogram provides a non-invasive diagnostic tool for risk stratification of clinical patients.

Background：Emerging evidence suggests that circular RNAs play critical roles in disease development especially in cancers. Previous genome-wide RNA-seq studies found that a circular RNA derived from SOD2 gene was highly upregulated in hepatocellular carcinoma (HCC), however, the role of circSOD2 in HCC remains largely unknown. Methods: The expression profiling of circSOD2 and microRNA in HCC patients were assessed by Real-Time Quantitative Reverse Transcription PCR (qRT-PCR). SiRNA or CRISPR-CAS9 were used to silence gene expression. The biological function of circSOD2 in HCC was investigated using in vitro and in vivo studies including, trans-well cell migration, cell apoptosis, cell cycle, CCK8, siRNA interference, western blots, and xenograft mouse model. The underlying molecular mechanism was determined by Chromatin Immunoprecipitation quantitative real time PCR (ChIP-qPCR), bioinformatic analysis, biotin-pull down, RNA immunoprecipitation, 5-mc DNA pulldown and luciferase assays. Results: In accordance with previous sequencing results, here, we demonstrated that circSOD2 was highly expressed in HCC tumor tissues compared with normal liver tissues. Mechanically, we showed that histone writer EP300 and WDR5 bind to circSOD2 promoter and trigger its promoter H3K27ac and H3K4me3 modification, respectively, which further activates circSOD2 expression. SiRNA mediated circSOD2 suppression impaired liver cancer cell growth, cell migration, prohibited cell cycle progression and in vivo tumor growth. By acting as a sponge, circSOD2 inhibits miR-502-5p expression and rescues miR-502-5p target gene DNMT3a expression. As a DNA methyltransferase, upregulated DNMA3a suppresses SOCS3 expression by increasing SOCS3 promoter DNA methylation. This event further accelerates SOCS3 downstream JAK2/STAT3 signaling pathway activation. In addition, we also found that activated STAT3 regulates circSOD2 expression in a feedback way. Conclusion: The novel signaling axis circSOD2/miR-502-5p/DNMT3a/JAK2/STAT3/circSOD2 provides a better understanding of HCC tumorigenesis. The molecular mechanism underlying this signaling axis offers new prevention and treatment of HCC.

Cholangiocarcinoma represents the second most common primary liver malignancy. The incidence rate has constantly increased over the last decades. Cholangiocarcinoma silent nature limits early diagnosis and prevents efficient treatment. Here we demonstrated that USP9X is downregulated in cholangiocarcinoma which contributes to tumorigenesis. The expression of USP9X in cholangiocarcinoma inhibited cell proliferation and colony formation in vitro as well as xenograft tumorigenicity in vivo. Clinical data demonstrated that expression levels of USP9X were positively correlated with favorable clinical outcomes. Mechanistic investigations further indicated that USP9X was involved in the deubiquitination of EGLN3, a member of 2-oxoglutarate and iron-dependent dioxygenases. USP9X elicited tumor suppressor role by preventing degradation of EGLN3. Importantly, knockdown of EGLN3 impaired USP9X-mediated suppression of proliferation. USP9X positively regulated the expression level of apoptosis pathway genes KIF1Bβ through EGLN3 thus involved in apoptosis of cholangiocarcinoma. Together, these findings help to understand that USP9X alleviates the malignant potential of cholangiocarcinoma through upregulation of EGLN3. Consequently, we provided novel insight into that USP9X is a potential biomarker or serves as a therapeutic or diagnostic target for cholangiocarcinoma.

Background : In this study, we comprehensively analyzed genes related to ferroptosis and iron metabolism to construct diagnostic and prognostic models and explore the relationship with the immune microenvironment in HCC. Methods : Integrated analysis, cox regression and the least absolute shrinkage and selection operator (LASSO) method of 104 ferroptosis- and iron metabolism-related genes and HCC-related RNA sequencing were performed to identify HCC-related ferroptosis and iron metabolism genes. Results : four genes (ABCB6, FLVCR1, SLC48A1 and SLC7A11) were identified to construct prognostic and diagnostic models. Poorer overall survival (OS) was exhibited in the high-risk group than that in the low-risk group in both the training cohort (P < 0.001, HR = 0.27) and test cohort (P < 0.001, HR = 0.27). The diagnostic models successfully distinguished HCC from normal samples and proliferative nodule samples. Compared with low-risk groups, high-risk groups had higher TMB; higher fractions of macrophages, follicular helper T cells, memory B cells, and neutrophils; and exhibited higher expression of CD83, B7H3, OX40 and CD134L. As an inducer of ferroptosis, erastin inhibited HCC cell proliferation and progression, and it was showed to affect Th17 cell differentiation and IL-17 signaling pathway through bioinformatics analysis, indicating it a potential agent of cancer immunotherapy. Conclusions : The prognostic and diagnostic models based on the four genes indicated superior diagnostic and predictive performance, indicating new possibilities for individualized treatment of HCC patients.